Although eosinophils as a group are readily identified by their unique morphology and staining properties, flow cytometry provides an important means for identification of subgroups based on differential expression of distinct surface Ags. Here, we characterize an eosinophil subpopulation defined by high levels of expression of the neutrophil Ag Gr1 (CD45CD11cSiglecFGr1). SiglecFGr1 eosinophils, distinct from the canonical SiglecFGr1 eosinophil population, were detected in allergen-challenged wild-type and granule protein-deficient (EPX and MBP-1) mice, but not in the eosinophil-deficient ΔdblGATA strain. In contrast to Gr1 neutrophils, which express both cross-reacting Ags Ly6C and Ly6G, SiglecFGr1 eosinophils from allergen-challenged lung tissue are uniquely Ly6G Although indistinguishable from the more-numerous SiglecFGr1 eosinophils under light microscopy, FACS-isolated populations revealed prominent differences in cytokine contents. The lymphocyte-targeting cytokines CXCL13 and IL-27 were identified only in the SiglecFGr1 eosinophil population (at 3.9 and 4.8 pg/10 cells, respectively), as was the prominent proinflammatory mediator IL-13 (72 pg/10 cells). Interestingly, bone marrow-derived (SiglecF), cultured eosinophils include a more substantial Gr1 subpopulation (∼50%); Gr1 bmEos includes primarily a single Ly6C and a smaller, double-positive (Ly6CLy6G) population. Taken together, our findings characterize a distinct SiglecFGr1 eosinophil subset in lungs of allergen-challenged, wild-type and granule protein-deficient mice. SiglecFGr1 eosinophils from wild-type mice maintain a distinct subset of cytokines, including those active on B and T lymphocytes. These cytokines may facilitate eosinophil-mediated immunomodulatory responses in the allergen-challenged lung as well as in other distinct microenvironments.

Purpose: To report a case of acute posterior multifocal placoid pigment epitheliopathy occurring in temporal association with multiple immunizations in a previously healthy 25year-old woman.Methods: Acute posterior multifocal placoid pigment epitheliopathy was diagnosed based on ophthalmological findings of bilateral placoid subretinal lesions complicated by a serous retinal detachment in the left eye.Results: Through HLA typing, the patient was found to possess the HLA-B*40 and HLA-DB1*15 alleles. She was treated with topical prednisolone acetate 1% and monitored for several months. The serous retinal detachment resolved, and visual acuity returned to normal.Conclusion: This case report adds to the body of knowledge regarding possible atypical interplay between vaccines and specific T-cell receptors of the host immune system and adds Polio and Tetanus to the growing list of vaccines potentially triggering acute posterior multifocal placoid pigment epitheliopathy. Increased awareness of the presentation of acute posterior multifocal placoid pigment epitheliopathy and that it may arise after immunization may also improve evaluation of acute changes in visual acuity.

Eosinophil-peroxidase (EPX) is a major constituent of the large cytoplasmic granules of both human and mouse eosinophilic leukocytes. Human EPX-deficiency is a rare, autosomal-recessive disorder limited to the eosinophil lineage. Our intent was to explore the impact of EPX gene-deletion on eosinophil content, structure and function. In response to repetitive intranasal challenge with a filtrate of the allergen, Alternaria alternata, we found significantly fewer eosinophils peripherally and in the respiratory tracts of EPX-/- mice compared to wild-type controls; furthermore, both the major population (Gr1-/lo) and the smaller population of Gr1hi eosinophils from EPX-/- mice displayed lower MFIs for Siglec F. Quantitative evaluation of transmission electron micrographs of lung eosinophils confirmed the relative reduction in granule outer matrix volume in cells from the EPX-/- mice, a finding analogous to that observed in human EPX deficiency. Despite the reduced size of the granule matrix, the cytokine content of eosinophils isolated from allergen-challenged EPX-/- and wild-type mice were largely comparable to one another, although the EPX-/- eosinophils contained reduced concentrations of IL-3. Other distinguishing features of lung eosinophils from allergen-challenged EPX-/- mice included a reduced fraction of surface TLR4-positive cells and reduced MFI for NOD1. Interestingly, the EPX gene-deletion had no impact on eosinophil-mediated clearance of gram-negative Hemophilius influenzae from the airways. As such, although no clinical findings have been associated with human EPX-deficiency, our findings suggest that further evaluation for alterations in eosinophil structure and function may be warranted.

Chronic inhalation of fungi and fungal components has been linked to the development of respiratory disorders, although their role with respect to the pathogenesis of acute respiratory virus infection remains unclear. Here, we evaluate inflammatory pathology induced by repetitive administration of a filtrate of the ubiquitous fungus, Alternaria alternata, and its impact on susceptibility to infection with influenza A. We showed previously that A. alternata at the nasal mucosae resulted in increased susceptibility to an otherwise sublethal inoculum of influenza A in wild-type mice. Here we demonstrate that A. alternata-induced potentiation of influenza A infection was not dependent on fungal serine protease or ribonuclease activity. Repetitive challenge with A. alternata prior to virus infection resulted proinflammatory cytokines, neutrophil recruitment, and loss of alveolar macrophages to a degree that substantially exceeded that observed in response to influenza A infection alone. Concomitant administration of immunomodulatory Lactobacillus plantarum, a strategy shown previously to limit virus-induced inflammation in the airways, blocked the exaggerated lethal response. These observations promote an improved understanding of severe influenza infection with potential clinical relevance for individuals subjected to continuous exposure to molds and fungi.